Targeting behavior of hepatic artery injected temperature sensitive liposomal adriamycin on tumor-bearing rats.
Temperature sensitive liposomal Adriamycin (LADM) was injected into the hepatic artery of rats bearing implanted hepatic tumors. Two hours after the injection, the liver was heated at 42 degrees C and maintained for six minutes at that temperature using local hyperthermia. Blood samples were taken at regular intervals until 8 hours after injection, at which time the animals were sacrificed and the drug distribution in the tissues was examined. Results indicate that the Adriamycin was released from the liposome, with the drug concentration in circulation peaking at 30 minutes after heating. High drug levels (25.2 micrograms/g of wet tissue) in the tumor and high tumor/liver Adriamycin level ratios (TLAR; 4.1) were found. The drug levels and the TLAR of the liposomal Adriamycin injection combined with heating (LADM H) were significantly different from those of the same dose of aqueous Adriamycin with heating (ADM H) or aqueous Adriamycin (ADM) and LADM without heating. The experiment shows that the LADM is cleared from the liver slowly, and when hyperthermia treatment at phase-transition temperature of the liposome is performed, the drug level in an implanted hepatic tumor is increased, and in the parenchyma is decreased. The results imply that targeting the hepatic tumor in this way may be an effective therapeutic method, and the drug release from the liposome may be controlled externally. This method appears promising for clinical practice.
Zou
Y Y
YY
Pharmaceutical Research Laboratory, Shenyang College of Pharmacy, China.
Ueno
M
M
Yamagishi
M
M
Horikoshi
I
I
Yamashita
I
I
Tazawa
K
K
Gu
X Q
XQ
D000818:Animals; D002279:Carcinoma 256, Walker / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D006499:Hepatic Artery; D006358:Hot Temperature; D007269:Injections, Intra-Arterial; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution / Q000502:physiology
D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin